CT-based evaluation of tissue expansion in cryoablation of ex vivo kidney.

OBJECTIVES: To evaluate tissue expansion during cryoablation, the displacement of markers in ex vivo kidney tissue was determined using computed tomographic (CT) imaging. METHODS: CT-guided cryoablation was performed in nine porcine kidneys over a 10 min period. Markers and fiber optic temperature probes were positioned perpendicular to the cryoprobe shaft in an axial orientation. The temperature measurement was performed simultaneously with the acquisitions of the CT images in 5 s intervals. The distance change of the markers to the cryoprobe was determined in each CT image and equated to the measured temperature at the marker. RESULTS: The greatest increase in the distance between the markers and the cryoprobe was observed in the initial phase of cryoablation. The maximum displacement of the markers was determined to be 0.31±0.2 mm and 2.8±0.02 %, respectively. CONCLUSIONS: The mean expansion of ex vivo kidney tissue during cryoablation with a single cryoprobe is 0.31±0.2 mm. The results can be used for identification of basic parameters for optimization of therapy planning.

Validating a simulation model for laser-induced thermotherapy using MR thermometry.

OBJECTIVES: We want to investigate whether temperature measurements obtained from MR thermometry are accurate and reliable enough to aid the development and validation of simulation models for Laser-induced interstitial thermotherapy (LITT). METHODS: Laser-induced interstitial thermotherapy (LITT) is applied to ex-vivo porcine livers. An artificial blood vessel is used to study the cooling effect of large blood vessels in proximity to the ablation zone. The experimental setting is simulated using a model based on partial differential equations (PDEs) for temperature, radiation, and tissue damage. The simulated temperature distributions are compared to temperature data obtained from MR thermometry. RESULTS: The overall agreement between measurement and simulation is good for two of our four test cases, while for the remaining cases drift problems with the thermometry data have been an issue. At higher temperatures local deviations between simulation and measurement occur in close proximity to the laser applicator and the vessel. This suggests that certain aspects of the model may need some refinement. CONCLUSION: Thermometry data is well-suited for aiding the development of simulations models since it shows where refinements are necessary and enables the validation of such models.

A thermometry software tool for monitoring laser-induced interstitial thermotherapy.

The purpose of this study was to develop a thermometry software tool for temperature monitoring during laser-induced interstitial thermotherapy (LITT). C++ programming language and several libraries including DICOM Toolkit, Grassroots DICOM library, Insight Segmentation and Registration Toolkit, Visualization Toolkit and Quasar Toolkit were used. The software's graphical user interface creates windows displaying the temperature map and the coagulation extent in the tissue, determined by the magnetic resonance imaging (MRI) thermometry with the echo planar imaging sequence and a numerical simulation based on the radiation and heat transfer in biological tissues, respectively. The software was evaluated applying the MRI-guided LITT to ex vivo pig liver and simultaneously measuring the temperature through a fiber-optic thermometer as reference. Using the software, the temperature distribution determined by the MRI method was compared with the coagulation extent simulation. An agreement was shown between the MRI temperature map and the simulated coagulation extent. Furthermore, the MRI-based and simulated temperatures agreed with the measured one - a correlation coefficient of 0.9993 and 0.9996 was obtained, respectively. The precision of the MRI temperature amounted to 2.4°C. In conclusion, the software tool developed in the present study can be applied for monitoring and controlling the LITT procedure in ex vivo tissues.

Cochlear pharmacokinetics with local inner ear drug delivery using a three-dimensional finite-element computer model.

HYPOTHESIS: Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. BACKGROUND: Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. METHODS: A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. RESULTS: For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. CONCLUSION: The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice.

Deterministic model for dose calculation in photon radiotherapy.

We present a model for dose calculation in photon radiotherapy based on deterministic transport equations. The model consists of two coupled equations, one for photon and one for electron transport and an equation for the absorbed dose. No assumptions are made with respect to the geometry or the homogeneity of the irradiated medium, so irradiation of any heterogenous medium can be simulated. To get a mathematically simpler model, approximations to the exact equations are presented which keep the essential physical contents of the exact equations, but which can be solved with less numerical effort. The results of dose calculations for simple examples are presented and discussed.

[1D-and 3D- computer simulation for experimental planning and interpretation of pharmacokinetic studies in the inner ear after local drug delivery]. / 1D- und 3D-Computersimulationen zur Versuchsplanung und -interpretation bei pharmakokinetischen Studien am Innenohr nach lokaler Medikamentenapplikation.

The local delivery of drugs to the cochlea is a promising alternative to systemic treatment of inner ear disorders. Whilst new drugs are being developed for this purpose, it is important to determine the time course and total dose required for the various target regions within the inner ear. Due to the small fluid spaces of the inner ear and the resulting experimental and analytical difficulties, many animal studies have only obtained one sample per animal. This results in limited information about drug time courses at specific locations in the inner ear. We show here how computer models considering general pharmacokinetic principles and inner ear geometry are used for application of the 3R-principle in animal research while avoiding experimental sampling artefacts. This can be achieved by: (1) careful planning and interpretation of experiments to study pharmacokinetics in the inner ear, (2) optimising volume sampling techniques, (3) facilitating the use of advantageous, continuous sampling methods like microdialysis and (4) developing a 3D-model that will permit consideration of the complex geometry of the inner ear when transferring results from one species to another.